title: Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis.
abstract: OBJECTIVE
  Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk.
  
  
  METHODS
  A Markov decision model with quality-of-life utility estimates for different MDS and transplantation states was assessed. Outcomes were life expectancy (LE) and quality-adjusted life expectancy (QALE). A total of 514 patients with de novo MDS aged 60 to 70 years were evaluated. Chronic myelomonocytic leukemia, isolated 5q- syndrome, unclassifiable, and therapy-related MDS were excluded. Transplantation using T-cell depletion or HLA-mismatched or umbilical cord donors was also excluded. RIC transplantation (n = 132) stratified by IPSS risk was compared with best supportive care for patients with nonanemic low/intermediate-1 IPSS (n = 123), hematopoietic growth factors for patients with anemic low/intermediate-1 IPSS (n = 94), and hypomethylating agents for patients with intermediate-2/high IPSS (n = 165).
  
  
  RESULTS
  For patients with low/intermediate-1 IPSS MDS, RIC transplantation LE was 38 months versus 77 months with nontransplantation approaches. QALE and sensitivity analysis did not favor RIC transplantation across plausible utility estimates. For intermediate-2/high IPSS MDS, RIC transplantation LE was 36 months versus 28 months for nontransplantation therapies. QALE and sensitivity analysis favored RIC transplantation across plausible utility estimates.
  
  
  CONCLUSIONS
  For patients with de novo MDS aged 60 to 70 years, favored treatments vary with IPSS risk. For low/intermediate-1 IPSS, nontransplantation approaches are preferred. For intermediate-2/high IPSS, RIC transplantation offers overall and quality-adjusted survival benefit.
authors.affiliation: Dana-Farber Cancer Institute, D1B05, 450 Brookline Ave, Boston, MA 02215, USA. jkoreth@partners.org
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Waleska S
authors.initials: WS
authors.lastname: Perez
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Sophie
authors.initials: S
authors.lastname: Park
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.forename: Lionel
authors.initials: L
authors.lastname: Ades
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Martin
authors.initials: M
authors.lastname: Jadersten
authors.forename: Eva
authors.initials: E
authors.lastname: Hellstrom-Lindberg
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
mesh_terms: D000368:Aged; D003661:Decision Support Techniques; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007391:International Cooperation; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000601:surgery*; D011788:Quality of Life; D019172:Transplantation Conditioning / Q000379:methods*